The diversity of potential biotherapeutic proteins is continuously rising as we elucidate the function of an ever-increasing number of secreted natural peptides. In addition, single-chain antibodies are showing promise as therapeutic agents for a variety of disease states. This profusion of potentially promising protein therapies demands improvements in the methods used for producing proteins on the scale necessary to meet demands for efficacy trials in animals and for use in the clinic. We have recently devised an episomal vector based upon a modified BPV replicon that can be maintained as a stable episome in a wide variety of cell types, including those currently used for large-scale protein production. in this application, we propose the adaptation of this vector for use in the manufacture of therapeutic plasma proteins. PROPOSED COMMERCIAL APPLICATIONS: Large-scale culture of mammalian cells remains the work-horse of therapeutic protein production. If the BPV-based system described herein can (1) reduce the time needed to generate a high-level producer cell line, (2) increase the stability of the cell line over time or (3) increase the overall amount of protein produced, then this system could be added directly as a module to the two systems most commonly used for protein manufacturing.